Process for the production of dibenzylsulphanilic acid



Patented July 23, 1940 UNITE-D stares PATENT orries PaooEss FOR THE. PRODUCTION OF DIBENZYLSULPHANILIG Aom Eugene A. Markush, Jersey Ci y, N. J., John J. Malawista, Brooklyn, N. Y., and Julius Miller, Newark, N. J., assignors to PharmaOhemical Corporation; New York, N. Y., a corporation of New York No Drawing. Application February 28, 1938,

Serial No. 192,962

11 Claims.

. to these known processes.

We have found that the above-mentioned objectionable features incident to the previously suggested processes result from the employment of strong alkalies during the production period and to the use of previously advised caustic alkali hydroxides, such as sodium hydroxide and potassium hydroxide.

We have further found that the above-described undesirable results are obtained by the use of caustic alkaline hydroxides even when the alkalinity of the reaction mass is maintained between pH 7.5 and pH 8.2, thus indicating that these objectionable results are produced by the employment of caustic alkaline hydroxides.

We have found that if the reaction between sulphanilic acid and benzyl chloride be conducted in the presence of mild acid-binding compounds instead of in the presence of caustic alkaline hydroxides, much greater yields of dibenzylsulphanilic acid with decreased quantities of monobenzylsulphanilic acid and unconverted sulphanilic acid are obtained than are producible by the former known processes.

We have further found that if the operation of our process be conducted in an alkalinity of between pH 7.5 and pH 8.3 almost theoretical yields of dibenzylsulphanilic acid are obtained with the production of practically no monobenzylsulphanilic acid and with practically no unconverted sulphanilic acid. -In fact we have thus obtained theoretical yields, and hence we prefer to maintain this degree of alkalinity in our process.

That the undesirable results of the previously known process are due to the employment of caustic alkaline hydroxides is shown by our extended experiments in which we have found that the successful results of our invention are not limited to the use of any particular chemical class of mild acid binding-compounds, but includes alkali earth hydroxides such as calcium hydroxide, magnesium hydroxide, strontium hydroxide, and tertiary amines such as pyridine, dimethyl aniline and triethanolamine, and hence by the Words mild acid-binding agents we mean those compounds which have mild acid-binding properties in contradistinction to those having strong caustic alkalinity such as sodium hy-' droxide and potassium hydroxide.

We give the following as examples of the process of our invention:

Example I The heretofore known processes for the production of dibenzylsulphanilic acid yield mixtures of sulphanilic acid, monobenzylsulphanilic acid and dibenzylsulphanilic acid. By using our process, theoretical yields and c. p. dibenzylsulphanilate is obtained. The purity is evidenced in the great improvement in shades obtained in conjunction with application of dyes.

173 parts sulphanilic acid suspended in 1000 parts water and 120 parts slaked lime added and the mixture is heated to reflux temperature.

278 parts benzyl chloride are added in portions so that the reaction proceeds smoothly. After all has been added, the boiling is continued for another 15 minutes and the excess benzylchloride distilled oif.

The reaction mass is then discharged into water and acidified to Congo with H01. Upon standing and stirring the mass crystallizes. The crystals are filtered and washed with dilute cold muriatic acid until free from calcium. The compound may then be either dried or converted to the metal salt by treating with the quantitative amount of metal hydroxide or carbonate. The yield is 353 parts of the free acid or 375 parts of the sodium salt.

Example II 173 grams of sulphanilic acid are suspended in 1000 c. c. of water and 395 grams dimethyl aniline added. The mixture is heated to reflux and 280 grams of benzyl chloride added in portions, allowing each portion to react before further addition. Refluxed one hour after all has been added. The reaction mass is allowed to cool to 80 C. and a strong sodium carbonate solution is carefully added until a slight test is obtained on phenolphthalein paper.

The dimethyl aniline is then blown off with steam and recovered. The residue is filtered and the filtrate evaporated to dryness. Yield, 370 grams sodium dibenzyl sulphanilate.

We do not limit ourselves to the particular chemicals, quantities, times, temperatures, alkalinities or other steps of procedure specifically mentioned as these are given simply as a means for clearly describing our invention.

What we claim is:

1. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols of benzyl chloride in the presence of an alkaline earth metal hydroxide.

2. A processfor the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols of benzyl chloride at an alkalinity between pH 7.5 and pH 8.3 in the presence of an alkaline earth metal hydroxide.

3. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols of benzyl chloride in the presence of a tertiary aromatic amine.

4. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols of benzyl chloride at an alkalinity between pH 7.5 and pH 8.3 in the presence of a tertiary aromatic amine.

5. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of slaked lime.

6. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of sulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of dimethylaniline.

8. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of dimethylaniline at an alkalinity between pH 7.5 and pH 8.3.

9. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of pyridine.

10. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of pyridine at an alkalinity between pH 7.5 and pH 8.3.

11. A process for the production of dibenzylsulphanilate which comprises reacting in boiling aqueous medium of one mol sulphanilic acid with 2 mols benzylchloride in the presence of mild acid binding agents selected from the group of alkaline earth metal hydroxides, pyridine, and tertiary aromatic amines.

EUGENE A. MARKUSI-l. JOHN J. MALAWISTA. JULIUS MILLER. 

